MiR-185 Targets the DNA Methyltransferases 1 and Regulates Global DNA Methylation in human gliomaReportar como inadecuado




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Molecular Cancer

, 10:124

First Online: 30 September 2011Received: 06 May 2011Accepted: 30 September 2011

Abstract

BackgroundPerturbation of DNA methylation is frequent in cancers and has emerged as an important mechanism involved in tumorigenesis. To determine how DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA immunoprecipitation MeDIP and Nimblegen CpG promoter microarrays to identify differentially DNA methylation sequences between primary glioma and normal brain tissue samples.

MethodsMeDIP-chip technology was used to investigate the whole-genome differential methylation patterns in glioma and normal brain tissues. Subsequently, the promoter methylation status of eight candidate genes was validated in 40 glioma samples and 4 cell lines by Sequenom-s MassARRAY system. Then, the epigenetically regulated expression of these genes and the potential mechanisms were examined by chromatin immunoprecipitation and quantitative real-time PCR.

ResultsA total of 524 hypermethylated and 104 hypomethylated regions were identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated regions were mapped to the promoters of known genes related to a variety of important cellular processes. Eight promoter-hypermethylated genes ANKDD1A, GAD1, HIST1H3E, PCDHA8, PCDHA13, PHOX2B, SIX3, and SST were confirmed in primary glioma and cell lines. Aberrant promoter methylation and changed histone modifications were associated with their reduced expression in glioma. In addition, we found loss of heterozygosity LOH at the miR-185 locus located in the 22q11.2 in glioma and induction of miR-185 over-expression reduced global DNA methylation and induced the expression of the promoter-hypermethylated genes in glioma cells by directly targeting the DNA methyltransferases 1.

ConclusionThese comprehensive data may provide new insights into the epigenetic pathogenesis of human gliomas.

KeywordsDNA methylation MiR-185 Glioma DNMT1 Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-10-124 contains supplementary material, which is available to authorized users.

Zuping Zhang, Hailin Tang contributed equally to this work.

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Autor: Zuping Zhang - Hailin Tang - Zeyou Wang - Baoxin Zhang - Wei Liu - Hongmei Lu - Lan Xiao - Xiaoping Liu - Rong Wang - Xia

Fuente: https://link.springer.com/







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